Inter-individual differences in the blood pressure lowering effects of dietary nitrate: a randomised double-blind placebo-controlled replicate crossover trial

Hayes, Eleanor, Alhulaefi, Shatha, Siervo, Mario, Whyte, Eleanor, Kimble, Rachel, Matu, Jamie, Griffiths, Alex, Sim, Marc, Burleigh, Mia, Easton, Chris, Lolli, Lorenzo ORCID: https://orcid.org/0000-0001-8670-3361, Atkinson, Greg, Mathers, John C. and Shannon, Oliver M. ORCID: https://orcid.org/0000-0001-8208-6837 (2025) Inter-individual differences in the blood pressure lowering effects of dietary nitrate: a randomised double-blind placebo-controlled replicate crossover trial. European Journal of Nutrition, 64 (2). 101. ISSN 1436-6207

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Abstract

Purpose: Dietary nitrate supplementation increases nitric oxide (NO) bioavailability and reduces blood pressure (BP). Inter-individual differences in these responses are suspected but have not been investigated using robust designs, e.g., replicate crossover, and appropriate statistical models. We examined the within-individual consistency of the effects of dietary nitrate supplementation on NO biomarkers and BP, and quantified inter-individual response differences. Methods: Fifteen healthy males visited the laboratory four times. On two visits, participants consumed 140 ml nitrate-rich beetroot juice (~ 14.0mmol nitrate) and, on the other two visits, they consumed 140 ml nitrate-depleted beetroot juice (~ 0.03mmol nitrate). Plasma nitrate and nitrite concentrations were measured 2.5 h post-supplementation. BP was measured pre- and 2.5 h post-supplementation. Between-replicate correlations were quantified for the placebo-adjusted post-supplementation plasma nitrate and nitrite concentrations and pre-to-post changes in BP. Within-participant linear mixed models and a meta-analytic approach estimated participant-by-condition treatment response variability. Results: Nitrate-rich beetroot juice supplementation elevated plasma nitrate and nitrite concentrations and reduced systolic (mean:-7mmHg, 95%CI: -3 to -11mmHg) and diastolic (mean:-6mmHg, 95%CI: -2 to -9mmHg) BP versus placebo. The participant-by-condition interaction response variability from the mixed model was ± 7mmHg (95%CI: 3 to 9mmHg) for systolic BP and consistent with the treatment effect heterogeneity t = ± 7mmHg (95%CI: 5 to 12mmHg) derived from the meta-analytic approach. The between-replicate correlations were moderate-to-large for plasma nitrate, nitrite and systolic BP (r = 0.55 to 0.91). Conclusions: The effects of dietary nitrate supplementation on NO biomarkers and systolic BP varied significantly from participant to participant. The causes of this inter-individual variation deserve further investigation. Trial registration: https://clinicaltrials.gov/study/NCT05514821.